Respiratory disorders related to airway inflammation include a number of severe lung diseases including asthma and chronic obstructive pulmonary disease (“COPD”). The airways of asthmatic patients are infiltrated by inflammatory leukocytes, of which the eosinophil is believed to be the most prominent component. Inflammatory sensitization of airway neurons is believed to increase nasal and cough sensitivity, heighten the sense of irritation, and promote fluid secretion, airway narrowing, and bronchoconstriction.
Various classes of drugs are currently being used for the treatment and/or prophylaxis of respiratory disorders like asthma and COPD. Some of the classes of such drugs are leukotriene receptor antagonists, β2-adrenergic agonists, anticholinergics and corticosteroids.
The TRPA1 receptor activation in the airways by noxious stimuli, including cold temperatures (generally, less than about 17° C.), pungent natural compounds (e.g., mustard, cinnamon and garlic), tobacco smoke, tear gas and environmental irritants, is supposed to be one of the mechanisms for neurogenic inflammation in the airways. Neurogenic inflammation is an important component of chronic airway diseases like COPD and asthma. Thus, TRPA1 antagonists are believed to play a role in the treatment of chronic airway diseases like COPD and asthma.
TRPA1 receptors are also found at the ends of sensory nerves and their activation results in painful sensations. Thus, TRPA1 antagonists are also believed to play a role in the treatment of pain.
PCT Application Publication Nos. WO 2011/043954, WO 2010/109334, WO 2010/109328 and WO 2010/141805 describe various transient receptor potential (“TRP”) receptor modulators.
U.S. Pat. Nos. 5,145,684 and 7,998,507, and PCT Application Publication No. WO2003/049718 disclose nanoparticulate compositions.
There is a need for new, improved formulations of TRPA1 antagonists and methods of making and using such formulations.